Treatment of hypercholesterolemia – high cholesterol levels

High cholesterol diet. Lifestyle and dietary changes remain key links in treatment, so all patients are advised to reduce their intake of saturated fat and cholesterol, increase physical activity and control weight. All patients should be advised to change their lifestyle, namely to reduce the intake of saturated fat less than 7% of the total caloric intake and cholesterol less than 200 mg / day, control weight, consume 10-25 g of dietary fiber per day, and increase physical activity. Diet change, of course, should occupy one of the leading places in lipid-lowering therapy, however, only diet can reduce LDL cholesterol levels by only 5-10%, and poor adherence to strict diets remains a significant problem in clinical practice. Ezetimive in the treatment of hypercholesterolemia Ezetimibe inhibits the absorption of cholesterol in the small intestine, which leads to a decrease in cholesterol reserves in the liver, and therefore enhances its excretion from the bloodstream. As monotherapy, the drug effectively reduces LDL cholesterol by 15-20%. The combination of ezetimibe and statins suppresses both the absorption of cholesterol and its production in the liver, which causes an additional reduction in LDL cholesterol levels by an additional 25% with potentially fewer side effects. Anion exchange resins in the treatment of high cholesterol Binding of anion exchange resins with bile acids leads to increased excretion of the latter with feces, which, in turn, increases the consumption of cholesterol in the liver for the synthesis of new bile acids. The increased consumption of cholesterol causes an increase in the number of LDL receptors in the liver to enhance the uptake of LDL from the bloodstream. On average, anion exchange resins lead to a decrease in the concentration of LDL by 15-30%.

The currently registered drugs are cholestyramine, colesevelam, and colestipol. Studies on the use of cholestyramine have shown a reduction in the risk of progression of atherosclerosis compared with the control group. Since resins are not systemic, they are practically safe, but can cause nausea, constipation, and flatulence. Other drugs (for example, warfarin, digoskin) should be taken 1 hour before or 4 hours after resin intake, as the latter can bind to them, reducing their absorption. Anion exchange resins are contraindicated in patients with hypertriglyceridemia, as they can significantly increase the level of TAG. Nicotinic acid and fibrates in hypercholesterolemia Nicotinic acid and fibric acid derivatives cause a moderate decrease in LDL (approximately 5-20%) and are mainly used to lower TAG and increase HDL, therefore, they are discussed in more detail in the section on the treatment of metabolic disorders of these lipoproteins. Even the most effective statins do not always achieve the target LDL cholesterol level. Increasing the dose of statins is associated with an increased risk of myopathies and liver damage. When statins are combined with ezetimibe, their effects are summed up, since both links of cholesterol metabolism are blocked at once. The increasing frequency of diabetes mellitus, insulin resistance and other metabolic disorders also testifies in favor of combination therapy that controls the level of various lipoproteins and all links of pathogenesis. Thus, the combination of statins and nicotinic acid, statins and fibric acid derivatives, or all three types of drugs at once may be the method of choice, especially in the treatment of patients with impaired HDL and TAG metabolism, although the safety issues of such combination therapy still require further study. Medication-free high cholesterol treatment LDL apheresis allows you to remove LDL directly from plasma. This method is indicated for severe, drug-resistant or refractory hyperlipidemia. The imposition of anastomosis between the proximal ileum and colon interrupts the intestinal-hepatic circulation of bile acids, which leads to an increase in the number of LDL receptors in the liver, followed by increased uptake of LDL from the bloodstream. This method can be recommended for patients with a pronounced increase in LDL, refractory to drug therapy, against the background of a normal TAG level if apheresis is impossible.

The effect of removing the thyroid gland on metabolism. Metabolism after thyroidectomy

One of the most characteristic effects of thyroid insufficiency is a decrease in basal metabolism, first noted by Magnus – Levy in 1895. A decrease in oxygen consumption at rest appears 5-7 days after removal of the thyroid gland and reaches a maximum in 3-5 weeks. In humans, the basal metabolism within 10 weeks after the complete removal of the gland falls by an average of 25%, although there are cases of its decrease by 40%. The decrease in oxygen consumption caused by thyroidectomy is accompanied by a corresponding decrease in nitrogen excretion. The specific dynamic effect normally provided by protein administration also drops sharply, but, at least in dogs, does not completely disappear. This does not occur due to a decrease in the activity of the body, but is the result of subtle shifts in cellular metabolism. A decrease in metabolism is also manifested by a slight decrease in body temperature. After thyroidectomy, a noticeable decrease in carbohydrate tolerance occurs: the introduction of a certain amount of glucose into the body leads to a more pronounced and prolonged increase in blood sugar than normal. However, despite such a decrease in tolerance, hyperglycemia and glucosuria are not observed in thyroidectomized animals on a normal diet. The drop in sugar tolerance in thyroid insufficiency appears to be a consequence of the loss of the liver’s ability to store carbohydrates. Thyroidectomized animals are less sensitive to the hypoglycemic effect of insulin than normal animals.

It is believed that thyroid hormone stimulates glycogenolysis in the liver. However, this effect, obviously, is not its primary action, but only a consequence of the general acceleration of oxidative reactions, along with the predominant use of carbohydrates, similar to what occurs during physical work. Patients with hyperthyroidism react to the introduction of carbohydrates (after their absorption) with very prolonged hyperglycemia and, sometimes, glucosuria. After an initial reaction, carbohydrates are easily utilized without excessive hyperglycemia and with a high respiratory rate. In both clinical and experimental hypothyroidism, the total content of fatty acids, phospholipids and cholesterol in serum is usually elevated. Complete thyroidectomy in humans can lead to an increase in cholesterol levels up to 300-400 mg%. However, patients with hyperthyroidism or thyroid insufficiency may also have normal serum cholesterol levels. This contradiction, possibly, is a consequence of significant differences in the normal content of cholesterol in the blood in different individuals, which determines the level from which it increases or decreases when the thyroid gland is dysfunctional. Thyroid dysfunction does not cause changes in free cholesterol / total cholesterol and total cholesterol / lipid phosphorus ratios. The level of cholesterol in the blood decreases with hyperthyroidism in parallel with a decrease in the content of phospholipids, as in case of malnutrition. In hypothyroidism, reverse shifts are observed.

Atherosclerosis of the coronary arteries in factory workers. Cholesterol and lecithin in the blood of workers Coronary artery atherosclerosis largely depends on lipoid and, in particular, cholesterol infiltration of the vessel walls. However, for the occurrence of cholesterol deposits in the arterial wall, the ratio of cholesterol and lecithin in the blood is of great importance. If in the blood the content of the former is significantly higher than the norm in comparison with the latter , then it falls out of the colloidal solution (N. N. Anichkov, A. L. Myasnikov, V. D. Tsinzerling, B. V. Ilyinsky). Research by Rainand and Pascvet showed that blood cholesterol levels in patients with atherosclerosis are highly variable, and it is not associated with the course of the disease itself. Morrisov cites the results of a three-year observation of 50 patients who have had myocardial infarction and were on a diet with a limited content of cholesterol and fats (20-25 g per day). The patients in this group showed an improvement in general health. Case came to the conclusion that the level of cholesterol in the blood of a person does not depend on the intake of cholesterol, if its content in food does not exceed 700 mg daily. The amount of this substance removed from the blood is proportional to its initial level.

According to many authors (M. S. Vovsi, A. L. Myasnikov, Klopotovsky, Keys, etc.), food cholesterol cannot be considered as the only cause of atherosclerosis. The body of animals and humans has the ability to synthesize cholesterol from the products of combustion of fats. In the patients examined by us with coronary cardiosclerosis with II degree coronary insufficiency in combination with hypertension, the ratio of cholesterol to lecithin in the blood was within the range (320-170 mg% cholesterol) / (240-200 mg% lecithin). In patients with coronary cardiosclerosis with degree I coronary insufficiency in combination with hypertension, this indicator was slightly lower: (280-155 mg% cholesterol) / (212-180 mg% lecithin) than in degree II coronary insufficiency. And, finally, in patients with grade I-II coronary insufficiency with normal arterial pressure, the blood cholesterol content was in the range of 230-125 mg%. We observed the same in patients with coronary cardiosclerosis with coronary insufficiency of II degree who had myocardial infarction: in those cases when the patients also suffered from hypertension, the combination of cholesterol and lecithin in the blood was within the range: (300-170 mg% cholesterol) / ( 265-185 mg% lecithin), and at normal blood pressure these figures fluctuated within the range: (230-122 mg% cholesterol) / (250-232 mg% lecithin). Despite the presence of II degree coronary insufficiency and myocardial infarction in the examined patients, their blood cholesterol levels varied within very different ranges: from normal (122-170 mg%) to higher (230-300 mg%), which significantly reduces the diagnostic value of this study. We also see that in some patients, the lecithin content in the blood was significantly higher than cholesterol, despite the pronounced atherosclerosis with coronary insufficiency of the II degree.

The use of triiodothyronine in diseases. Effects of triiodothyronine metabolites

Administration of triiodothyronine to patients with Graves’ disease at a dose of 60-200 y for 7 days leads to a 24% decrease in the content of radioactive iodine, while a dose of 2 mg daily has no effect. According to a number of researchers (Goolden, Burrel), the human body needs 75-100 L-triiodothyronine per day to remain in a normal state; 20 μg triiodothyronine equals 0.1 mg L-thyroxine or 65 mg thyroid extract. Triiodothyronine gives a quick effect in hypothyroidism or myxedema, when the patient receives 100-400 micrograms per day. Maintenance treatment is 40 y per day. Studies with d-triiodothyronine in thyroidectomized patients show that the maintenance dose is approximately 150 mcg per day. For myxedema coma, give a dose of 80 mcg intravenously per day and at the same time 20 under the tongue every 4 hours. After 12 hours, the patient begins to recover. In case of endemic goiter, treatment with triiodothyronine is more beneficial because triiodothyronine is 7 times more active than thyroxine (Starr). If the transformation of thyroxine into triiodothyronine is disturbed due to congenital deiodase deficiency, the administration of triiodothyronine will give a positive effect (Rigss). With endemic goiter, hypothyroidism and cretinism and a lack of deiodase, the administration of triiodothyronine also gives a good result. Of the thyroxine derivatives tested, 3,5-diiodothyroacetic acid (DIAA) has the greatest effect on blood cholesterol and lipids, without affecting oxygen consumption and growth (Lerman). Triiodothyroacetic and tetraiodothyroacetic acids were also studied. It turned out that they affect the growth and consumption of oxygen by tissues and simultaneously reduce cholesterolemia in both myxedema and thyroidectomized animals. However, their influence is passing. More active from this point of view is diiodothyroacetic acid. It was found that the introduction of DIAK does not affect the absorption of cholesterol-C14. Cholesterol and lipids leave the liver depot. According to Duncan and Best, these most active substances can lower cholesterol levels. Among them are derivatives of formic acid thyroxine. Thus, tetraiodothyroformolic acid is more active in producing hypocholesterolemia than thyroxine. Subcutaneous administration of tetraiodothyreoacetic acid to animals on a diet rich in cholesterol lowers blood cholesterol levels. Duncan and Best also found DIAA and diiodothyroformolic acid to be more active in lowering plasma and liver cholesterol concentrations, without significantly affecting BMR and growth.

Large doses of triiodothyreopropionic acid administered by mouth (1-8 mg per day) also significantly reduce the amount of cholesterol in the serum and liver, but increase the basal metabolism both in hypothyroidism and in the case of thyrsoidectomy. The most active derivatives that reduce the amount of cholesterol in the blood include in their structure diphenylether, which contains iodine in positions 3 and 5, a lateral chain, carboxylic acid with 1-2 carbohydrates, and a phenol group in ring B in the para position. The distribution and turnover time of some derivatives, such as triiodothyroacetic acid and tetraiodothyroacetic acid in humans, were also studied. Triiodothyroacetic acid J131 disappears after about 18 hours. In patients with biliary fistula, the highest concentration of these substances in bile was noted. J131-labeled tetraiodothyroacetic and triiodothyroacetic acids are converted to other substances. So, in plasma, tetraiodothyroacetic acid and small amounts of iodides appear as the main component, and in urine – iodides in small amounts, triiodoacetic acid in large amounts. Tetraiodothyroacetic acid is rapidly excreted from the blood, concentrated in the liver and excreted from the body as a compound with carbohydrates. Compared with triiodothyroacetic acid, tetraiodothyroacetic acid is metabolized more slowly, carbohydrate compounds are formed slowly. The introduction of these substances reduces cholesterolemia in myxedema patients after two weeks, increases creatinuria, normalizes the electrocardiogram, and reduces weight. However, their basic metabolic rate changes. These substances affect not only the activity of peroxidase and cytochrome oxidase in the cells of the thyroid gland, but also the same enzymes of other cells of the body (Lerman). It should be noted that antithyroid substances pass through the placental barrier, thus affecting the thyroid gland of the embryo. Some researchers point to the effect of these substances on the central nervous system. So, Goldsmith and Gordon, Barnett and Hughes caused phenomena similar to cretinism in rats, whose mothers were injected with thiouracil during pregnancy. Marzulo and Russo indicate the appearance of degenerative changes at the level of hypothalamic nerve cells in pigeons after administration of methylthiouracil. According to Milcu and co-workers, the administration of methylthiouracil to animals during pregnancy causes bleeding and spontaneous abortion, which leads to decreased fertility. The study of the central nervous system revealed extensive cellular and metabolic disorders that predominate in the cerebral cortex and hypothalamus. In the cerebral cortex, parenchymal disorders resembling the phenomena of encephalitis were found . In other areas, cell differentiation delay, hyperplasia, neurolysis, spongy degeneration and vasodilation were noted. According to Costa, Catino, Ferarris, and others, radioactive iodine is more quickly fixed in the thyroid gland in nerds than in hypothyroids. The secretion of iodoproteins in cretins is reduced, but still higher than in myxedema patients. Cholesterol and basal metabolic rate in nerds are almost normal. Therefore, cretinism and myxedema, despite the fact that they have many points of contact, are still two different forms of hypothyroidism.

local_offerevent_note November 18, 2020

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